Trial Outcomes & Findings for FUTURE 3 Study Extension (NCT NCT01338415)

Last Updated: 2025-03-30

Results Overview

This is the total number of subjects with at least one adverse event (serious or not serious) whether or not causally related to the study drug and presented cumulatively in the FUTURE 3 and FUTURE 3 Extension study. NOTE: FUTURE 3 extension study was exploratory and no primary efficacy and safety endpoints were defined in the protocol. So, this safety outcome measure was selected and reported as primary endpoint here.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

58 participants

Primary outcome timeframe

Up to 62 weeks in average

Results posted on

2025-03-30

Participant Flow

Participants in this 1-year extension study were pediatric patients who completed the 6-month randomized open-label core study AC-052-373. In addition, patients were required to have tolerated study treatment during the FUTURE 3 core study and were considered by the investigator to benefit from continued bosentan treatment.

64 patients were randomized in the FUTURE 3 core study, among whom 58 were enrolled in the FUTURE 3 extension study. Of the 58 participants in the FUTURE 3 extension study, a total of 10 participants entered the exceptional use treatment period (EUTP). Data for 3 participants in China after 19 Nov 2019 was not included in the report to meet the Human Genetic Resources Administration Office (HGRAO) requirements.

Participant milestones

Participant milestones
Measure	Bosentan 2mg/kg b.i.d. Patients received 2 milligrams per kilogram (mg/kg) bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Bosentan 2mg/kg t.i.d. Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Bosentan 2mg/kg b.i.d or t.i.d. During EUTP Participants who entered the exceptional use treatment period (EUTP), continued receiving 2 mg/kg bosentan b.i.d or t.i.d up to Amendment B. After implementation of Amendment B, all participants received 2 mg/kg bosentan b.i.d.
Core + Extension STARTED	33	31	0
Core + Extension Enrolled in FUTURE 3 Extension	31	27	0
Core + Extension COMPLETED	23	22	0
Core + Extension NOT COMPLETED	10	9	0
Exceptional Use Treatment Period STARTED	0	0	10
Exceptional Use Treatment Period COMPLETED	0	0	4
Exceptional Use Treatment Period NOT COMPLETED	0	0	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Bosentan 2mg/kg b.i.d. Patients received 2 milligrams per kilogram (mg/kg) bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Bosentan 2mg/kg t.i.d. Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Bosentan 2mg/kg b.i.d or t.i.d. During EUTP Participants who entered the exceptional use treatment period (EUTP), continued receiving 2 mg/kg bosentan b.i.d or t.i.d up to Amendment B. After implementation of Amendment B, all participants received 2 mg/kg bosentan b.i.d.
Core + Extension Adverse Event	8	6	0
Core + Extension Withdrawal by Subject	1	1	0
Core + Extension Other (PAH not the main etiology of PH)	0	2	0
Core + Extension Other (administrative reason)	1	0	0
Exceptional Use Treatment Period Administrative decision	0	0	1
Exceptional Use Treatment Period Ongoing at the cut-off date of 19 Nov 2019	0	0	3
Exceptional Use Treatment Period Withdrawal by Subject	0	0	1
Exceptional Use Treatment Period Death	0	0	1

Baseline Characteristics

FUTURE 3 Study Extension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bosentan 2mg/kg b.i.d. n=33 Participants Patients received 2 milligrams per kilogram (mg/kg) bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Bosentan 2mg/kg t.i.d. n=31 Participants Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Total n=64 Participants Total of all reporting groups
Age, Continuous	4.5 years STANDARD_DEVIATION 3.35 • n=93 Participants	5.2 years STANDARD_DEVIATION 3.81 • n=4 Participants	4.8 years STANDARD_DEVIATION 3.57 • n=27 Participants
Age, Customized Age Categories as per protocol · Infants and toddlers (28 days-23 months)	10 Participants n=93 Participants	11 Participants n=4 Participants	21 Participants n=27 Participants
Age, Customized Age Categories as per protocol · Children (2-11 years)	23 Participants n=93 Participants	20 Participants n=4 Participants	43 Participants n=27 Participants
Sex: Female, Male Female	18 Participants n=93 Participants	10 Participants n=4 Participants	28 Participants n=27 Participants
Sex: Female, Male Male	15 Participants n=93 Participants	21 Participants n=4 Participants	36 Participants n=27 Participants
Race/Ethnicity, Customized Race as per protocol · Caucasian/White	25 Participants n=93 Participants	23 Participants n=4 Participants	48 Participants n=27 Participants
Race/Ethnicity, Customized Race as per protocol · Black	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants
Race/Ethnicity, Customized Race as per protocol · Asian	6 Participants n=93 Participants	4 Participants n=4 Participants	10 Participants n=27 Participants
Race/Ethnicity, Customized Race as per protocol · Hispanic	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized Race as per protocol · Other	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Pulmonary Arterial Hypertension (PAH) etiology Idiopathic	14 Participants n=93 Participants	15 Participants n=4 Participants	29 Participants n=27 Participants
Pulmonary Arterial Hypertension (PAH) etiology Heritable	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants
Pulmonary Arterial Hypertension (PAH) etiology Congenital heart disease	6 Participants n=93 Participants	2 Participants n=4 Participants	8 Participants n=27 Participants
Pulmonary Arterial Hypertension (PAH) etiology Associated PAH (i.e.,PAH after surgery for CHD)	11 Participants n=93 Participants	13 Participants n=4 Participants	24 Participants n=27 Participants
Pulmonary Arterial Hypertension (PAH) etiology Missing	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
World Health Organization functional class (WHO FC) FC I	9 Participants n=93 Participants	10 Participants n=4 Participants	19 Participants n=27 Participants
World Health Organization functional class (WHO FC) FC II	12 Participants n=93 Participants	15 Participants n=4 Participants	27 Participants n=27 Participants
World Health Organization functional class (WHO FC) FC III	12 Participants n=93 Participants	6 Participants n=4 Participants	18 Participants n=27 Participants

PRIMARY outcome

Timeframe: Up to 62 weeks in average

Population: The analysis was performed on the Safety population analysis set, including all patients who received at least one dose of study treatment and evaluated according to the study treatment that they received.

Outcome measures

Outcome measures
Measure	Bosentan 2mg/kg b.i.d. n=33 Participants Patients received 2 milligrams per kilogram (mg/kg) bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Bosentan 2mg/kg t.i.d. n=31 Participants Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.
Treatment Emergent Adverse Events (AEs) up to 7 Days After Permanent Study Drug Discontinuation	29 Participants	26 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: At Month 12

Population: The intent to treat population was used. Where a missing visit score exists between two visits with scores, the missing score was imputed with the worse score of the non-missing scores; if the missing score was not between 2 visits with scores, it was replaced by the last non-missing score.

The WHO FC indicates the severity of Pulmonary Arterial Hypertension: class I (none) to class IV (most severe). Changes from baseline to month 12 and month 18 of treatment with bosentan included: improvement (change from a higher to a lower FC), worsening (change from a lower to a higher FC) or no change/stable (same FC at baseline and at the post-baseline time point). Baseline was defined as the last valid assessment performed prior to first study drug intake in the FUTURE 3 core study.

Outcome measures

Outcome measures
Measure	Bosentan 2mg/kg b.i.d. n=33 Participants Patients received 2 milligrams per kilogram (mg/kg) bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Bosentan 2mg/kg t.i.d. n=31 Participants Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.
Change From Baseline up to 12 Months of Study Treatment in the World Health Organization Functional Classification (WHO FC) Stable WHO FC	22 Participants	25 Participants
Change From Baseline up to 12 Months of Study Treatment in the World Health Organization Functional Classification (WHO FC) Improved WHO FC	7 Participants	3 Participants
Change From Baseline up to 12 Months of Study Treatment in the World Health Organization Functional Classification (WHO FC) Worsened WHO FC	4 Participants	3 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: At Month 18

Outcome measures

Outcome measures
Measure	Bosentan 2mg/kg b.i.d. n=33 Participants Patients received 2 milligrams per kilogram (mg/kg) bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Bosentan 2mg/kg t.i.d. n=31 Participants Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.
Change From Baseline up to 18 Months of Study Treatment in the World Health Organization Functional Classification (WHO FC) Stable WHO FC	25 Participants	25 Participants
Change From Baseline up to 18 Months of Study Treatment in the World Health Organization Functional Classification (WHO FC) Improved WHO FC	3 Participants	3 Participants
Change From Baseline up to 18 Months of Study Treatment in the World Health Organization Functional Classification (WHO FC) Worsened WHO FC	5 Participants	3 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: At Month 12

Population: The intent to treat population was used for these analyses. No imputation method was used. Only patients with available results at the corresponding time point are included in the analysis.

The GCIS is a scale used to rate the patient's current overall clinical condition ("Very Good", "Good", "Neither Good or Bad", "Bad", and "Very Bad"). Rating was performed independently by the physician and parents or legal representatives. Baseline was defined as the last valid assessment performed prior to first study drug intake in the FUTURE 3 core study.

Outcome measures

Outcome measures
Measure	Bosentan 2mg/kg b.i.d. n=28 Participants Patients received 2 milligrams per kilogram (mg/kg) bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Bosentan 2mg/kg t.i.d. n=23 Participants Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.
Change From Baseline up to 12 Months of Study Treatment in the Global Clinical Impression Scale (GCIS) Assessment by Physician · Stable	16 Participants	16 Participants
Change From Baseline up to 12 Months of Study Treatment in the Global Clinical Impression Scale (GCIS) Assessment by Physician · Improved	10 Participants	6 Participants
Change From Baseline up to 12 Months of Study Treatment in the Global Clinical Impression Scale (GCIS) Assessment by Physician · Worsened	2 Participants	1 Participants
Change From Baseline up to 12 Months of Study Treatment in the Global Clinical Impression Scale (GCIS) Assessment by Parents/Legal representative · Stable	16 Participants	12 Participants
Change From Baseline up to 12 Months of Study Treatment in the Global Clinical Impression Scale (GCIS) Assessment by Parents/Legal representative · Improved	9 Participants	11 Participants
Change From Baseline up to 12 Months of Study Treatment in the Global Clinical Impression Scale (GCIS) Assessment by Parents/Legal representative · Worsened	3 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: At Month 18

Population: The intent to treat population was used. No imputation method was used. Only patients with available results at the corresponding time point are including in the analysis.

Outcome measures

Outcome measures
Measure	Bosentan 2mg/kg b.i.d. n=19 Participants Patients received 2 milligrams per kilogram (mg/kg) bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Bosentan 2mg/kg t.i.d. n=18 Participants Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.
Change From Baseline up to 18 Months of Study Treatment in the Global Clinical Impression Scale (GCIS) Assessment by Physician · Stable	9 Participants	12 Participants
Change From Baseline up to 18 Months of Study Treatment in the Global Clinical Impression Scale (GCIS) Assessment by Physician · Improved	6 Participants	5 Participants
Change From Baseline up to 18 Months of Study Treatment in the Global Clinical Impression Scale (GCIS) Assessment by Physician · Worsened	4 Participants	1 Participants
Change From Baseline up to 18 Months of Study Treatment in the Global Clinical Impression Scale (GCIS) Assessment by Parents/Legal representative · Stable	8 Participants	7 Participants
Change From Baseline up to 18 Months of Study Treatment in the Global Clinical Impression Scale (GCIS) Assessment by Parents/Legal representative · Improved	6 Participants	10 Participants
Change From Baseline up to 18 Months of Study Treatment in the Global Clinical Impression Scale (GCIS) Assessment by Parents/Legal representative · Worsened	5 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 62 weeks in average

Population: The intent to treat population was used

Number of patients with at least one PAH-worsening component (death, lung transplant, hospitalization due to PAH progression, initiation of new therapy for PAH, new/worsening right heart failure) reported cumulatively over FUTURE 3 core and extension study.

Outcome measures

Outcome measures
Measure	Bosentan 2mg/kg b.i.d. n=33 Participants Patients received 2 milligrams per kilogram (mg/kg) bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Bosentan 2mg/kg t.i.d. n=31 Participants Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.
Number of Patients With Pulmonary Arterial Hypertension (PAH) Worsening Components up to the Last Day of Treatment + 7 Days At least one PAH-worsening event	10 Participants	5 Participants
Number of Patients With Pulmonary Arterial Hypertension (PAH) Worsening Components up to the Last Day of Treatment + 7 Days No PAH-worsening event	23 Participants	26 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to Month 18

Population: These are the numbers of patients at risk at the time of study treatment initiation in the FUTURE 3 core study

PAH progression was defined by time elapsed from the first study drug administration in the FUTURE core study to the day of the first occurrence of any of the following PAH worsening events: death, lung transplant, hospitalization due to PAH progression, initiation of new therapy for PAH or new / worsening right heart failure. Subjects without a PAH worsening event were censored at EOT + 7 days. PAH progression was estimated by Kaplan-Meier methodology and expressed by the percentage of participants free of events at different time points.

Outcome measures

Outcome measures
Measure	Bosentan 2mg/kg b.i.d. n=33 Participants Patients received 2 milligrams per kilogram (mg/kg) bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Bosentan 2mg/kg t.i.d. n=31 Participants Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.
Pulmonary Arterial Hypertension (PAH) Progression up to End of Treatment + 7 Days Kaplan-Meier estimate at Month 12	74.9 Percentage of patients free of events Interval 56.0 to 86.6	88.9 Percentage of patients free of events Interval 69.4 to 96.3
Pulmonary Arterial Hypertension (PAH) Progression up to End of Treatment + 7 Days Kaplan-Meier estimate at Month 18	68.2 Percentage of patients free of events Interval 48.9 to 81.5	81.0 Percentage of patients free of events Interval 60.1 to 91.7

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to month 18

Population: These are the numbers of patients at risk at the time of study treatment initiation in the FUTURE 3 core study

Overall survival was defined as the time elapsed between the first study drug administration and death (any cause) up to end of study (Month 18 survival follow-up), regardless of whether the patient was on study treatment. Patients who died, regardless of the cause of death, were considered to have had an event. Patients last known to have been alive were censored on their date of last contact. Percentage of participants without death at different time points was estimated using Kaplan-Meier methodology.

Outcome measures

Outcome measures
Measure	Bosentan 2mg/kg b.i.d. n=33 Participants Patients received 2 milligrams per kilogram (mg/kg) bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Bosentan 2mg/kg t.i.d. n=31 Participants Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.
Overall Survival Kaplan-Meier estimate at Month 12	81.8 Percentage of participants Interval 63.9 to 91.4	90.0 Percentage of participants Interval 72.1 to 96.7
Overall Survival Kaplan-Meier estimate at Month 18	75.8 Percentage of participants Interval 57.3 to 87.1	86.5 Percentage of participants Interval 68.0 to 94.7

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 7 days after discontinuation of study drug (up to 3 years and 4 months)

Population: Exceptional-use set included all patients who entered the EUTP. Due to change in study conduct, patients treated with bosentan t.i.d. switched to b.i.d. after local Amendment B to global protocol version 2 (17 March 2015 for Belarus and Ukraine, 1 April 2015 for China) and displaying summaries in the EUTP period by dose were not significant. Therefore, the results were reported combined for bosentan b.i.d./t.i.d.

Outcome measures

Outcome measures
Measure	Bosentan 2mg/kg b.i.d. n=10 Participants Patients received 2 milligrams per kilogram (mg/kg) bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Bosentan 2mg/kg t.i.d. Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.
Exceptional Use Treatment Period (EUTP): Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) up to 7 Days After Permanent Discontinuation of Study Drug	80 percentage of participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 7 days after discontinuation of study drug (up to 3 years and 4 months)

An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAE are defined as AEs with onset during the treatment period or that are a consequence of a pre-existing condition that has worsened since baseline. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Outcome measures

Outcome measures
Measure	Bosentan 2mg/kg b.i.d. n=10 Participants Patients received 2 milligrams per kilogram (mg/kg) bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Bosentan 2mg/kg t.i.d. Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.
EUTP: Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs) up to 7 Days After Permanent Discontinuation of Study Drug	40 percentage of participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 years and 4 months

Outcome measures

Outcome measures
Measure	Bosentan 2mg/kg b.i.d. n=10 Participants Patients received 2 milligrams per kilogram (mg/kg) bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Bosentan 2mg/kg t.i.d. Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.
EUTP: Percentage of Participants With AEs Leading to Premature Discontinuation of Study Drug	0 percentage of participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: From 7 up to 60 days after permanent discontinuation of study drug (up to 3 years and 4 months)

A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Outcome measures

Outcome measures
Measure	Bosentan 2mg/kg b.i.d. n=10 Participants Patients received 2 milligrams per kilogram (mg/kg) bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Bosentan 2mg/kg t.i.d. Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.
EUTP: Percentage of Participants With SAEs From 7 up to 60 Days After Permanent Discontinuation of Study Drug	0 percentage of participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 7 days after discontinuation of study drug (up to 3 years and 4 months)

Percentage of participants with deaths were reported.

Outcome measures

Outcome measures
Measure	Bosentan 2mg/kg b.i.d. n=10 Participants Patients received 2 milligrams per kilogram (mg/kg) bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Bosentan 2mg/kg t.i.d. Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.
EUTP: Percentage of Participants With Deaths	10 percentage of participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 7 days after discontinuation of study drug (up to 3 years and 4 months)

Percentage of participants with AESI including liver abnormalities and anemia were reported.

Outcome measures

Outcome measures
Measure	Bosentan 2mg/kg b.i.d. n=10 Participants Patients received 2 milligrams per kilogram (mg/kg) bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Bosentan 2mg/kg t.i.d. Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.
EUTP: Percentage of Participants With Adverse Events of Special Interest (AESI)	20 percentage of participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 7 days after discontinuation of study drug (up to 3 years and 4 months)

Percentage of participants with treatment-emergent marked laboratory abnormalities were reported.

Outcome measures

Outcome measures
Measure	Bosentan 2mg/kg b.i.d. n=10 Participants Patients received 2 milligrams per kilogram (mg/kg) bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Bosentan 2mg/kg t.i.d. Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.
EUTP: Percentage of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 7 Days After Permanent Discontinuation of Study Drug	0 percentage of participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 7 days after discontinuation of study drug (up to 3 years and 4 months)

Percentage of participants with liver function abnormalities: Alanine aminotransferase (ALT) greater than (\>)3\*upper limit of normal (ULN), ALT/aspartate aminotransferase (AST) \>3\*ULN, ALT /AST \>3\*ULN and less than or equal to (\<=) 5\*ULN, ALT/AST \>5\*ULN and \<=8\*ULN, ALT/AST \>8\*ULN and ALT/AST \>3\*ULN, total bilirubin \>2\*ULN and alkaline phosphatase (ALP) \<=2\*ULN were reported.

Outcome measures

Outcome measures
Measure	Bosentan 2mg/kg b.i.d. n=10 Participants Patients received 2 milligrams per kilogram (mg/kg) bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Bosentan 2mg/kg t.i.d. Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.
EUTP: Percentage of Participants With Liver Function Abnormalities	0 percentage of participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, up to 7 days after end of treatment (up to 3 years and 4 months)

Percentage of participants with any time occurrence of hemoglobin (Hgb) less than or equal to (\<=) 10 g/dL and 8 g/dL between baseline and up to the last day of treatment + 7 days during EUTP were reported. Here "N" (number of subjects analyzed) signifies subjects who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Bosentan 2mg/kg b.i.d. n=9 Participants Patients received 2 milligrams per kilogram (mg/kg) bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.	Bosentan 2mg/kg t.i.d. Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study.
EUTP: Percentage of Participants With Any Time Occurrence of Hemoglobin <=10 Gram Per Deciliter (g/dL) and <=8g/dL Between Baseline and up to 7 Days After End of Treatment (EOT) Hgb <=10 g/dL	22.2 percentage of participants	—
EUTP: Percentage of Participants With Any Time Occurrence of Hemoglobin <=10 Gram Per Deciliter (g/dL) and <=8g/dL Between Baseline and up to 7 Days After End of Treatment (EOT) Hgb <=8 g/dL	0 percentage of participants	—

Adverse Events

Bosentan 2mg/kg b.i.d.

Serious events: 15 serious events

Other events: 24 other events

Deaths: 8 deaths

Bosentan 2mg/kg t.i.d

Serious events: 13 serious events

Other events: 23 other events

Deaths: 4 deaths

Bosentan 2mg/kg b.i.d or t.i.d. During EUTP

Serious events: 4 serious events

Other events: 8 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Principal Clinical Scientist

Actelion Pharmaceuticals Ltd

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Any study-related article or abstract written independently by investigators must be submitted to Actelion for review at least 60 days prior to submission for publication or presentation.
Publication restrictions are in place

Restriction type: OTHER